Fasudil is found to reverse key symptoms of schizophrenia in mice
nagoya-u.ac.jp
nagoya-u.ac.jp
The symptoms are: - Reduced density of pyramidal neurons - Cognitive dysfunction associated with methamphetamine treatment
Schizophrenia and the related schizotaxia (a condition that is conjectured to be present in anyone who is schizophrenic) has a number of hidden phenotypes however, such as deficits in eye tracking
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212396/
something like that must be detectable in animal models.
As usual, wake me when there are promising results in humans that actually manifest the condition.
One of the foundational studies supporting SSRIs involved a model of "depression" which was regularly delivering electric shocks to mice. So SSRIs provide statistically significant improvements for mice being mildly tortured.
To be fair, this is probably a good model of what lots of people on SSRIs actually have as a life experience.
"Chemical imbalance", my ass.
I'm no expert, but this measure would seem to have innumerable potential confounds. I guess it was chosen because it's fast to carry out.
The correct answer is we don't know why SSRIs work, which isn't unusual for medicine.
It's not just a pop science myth, and there are, somehow, still many professionals who think it is or could be a good explanation.
[1]: https://theconversation.com/depression-is-probably-not-cause...
https://en.wikipedia.org/wiki/Serotonin_transporter
Now what happens after you block the serotonin transporter and how that leads to relieved symptoms of depression and anxiety, that's much more controversial. There is a strong association between social dominance and serotonin, and "low serotonin levels" are associated with being an underdog. It's a reasonable assumption that SSRIs attenuate stress-related brain damage caused by being an underdog.
https://www.nature.com/articles/s41598-018-33410-1
https://link.springer.com/article/10.1007/s00213-002-1049-7
You don't hear that one very much because if you took it seriously it would mean you shouldn't take a pill but rather you should join a revolutionary party.
Obviously there's no way to just become someone who can feel successful, but having social hobbies is a more normal way to get there. But if you're depressed you have a harder time doing that.
It's probably not what SSRIs are doing though. It might be something BDNF related, or brain inflammation (everything's inflammation…).
https://www.science.org/content/blog-post/how-antidepressant...
Interesting.
I converted the energy per mass the mice had been exposed for and found it wasn't far off what a microwave meal receives (and in similar frequency range). Hardly a shocker that wasn't healthy for the mice. Far cry from a mobile phone tho.
In this case, neural damage is induced through methamphetamine, this is thought to damage some of the same neurons that schizophrenia affects.
The results may or may not transfer to the actual disease in human. There's a reason most animal based research doesn't pan out in the end.
It might be more accurate to say its accepted that it may be involved in particular cases, but is not a general feature in all cases, nor is it determinative (i.e. some genetic makeups may be correlated with a higher risk of schizophrenia, but only by a small factor, and many people with such genetic makeups never develop the condition). This is an area of active debate whose outcome remains uncertain. For example (2021):
"Schizophrenia: a classic battle ground of nature versus nurture debate", Clair & Lang
https://sci-hub.se/10.1016/j.scib.2021.01.032
Note that twin studies are heavily skewed by shared environmental conditions and so are not that valid of an argument regarding genetic determinism (in this as well as many other psychiatric conditions). The current state seems to be:
> "However, little is known about the causal biochemical and molecular mechanisms involved that translate genetic and environmental risk into the schizophrenia phenotype. It is also now clear that environmental exposures that increase the risk of schizophrenia can occur at any point across the life span and probably include pre-conceptional exposure."
This is probably a case where mice studies are not very relevant to the human condition.
My father's siblings also have various conditions ranging from BPD, Narcissistic PD, and schizotypal personality disorder. Many of them grew up in different environments. Me and my children grew up in different continents and social structures altogether.
It’s pretty well accepted that bipolar and schizophrenia are both highly inheritable. It’s also known that not everyone with the genes develops the disorder. Environment is thought to play a significant part here in the disorder appearing.
Both disorders are known to get worse if left untreated. For some people, it’s a matter of sufficient time or stress before the disorder appears. In my case, I started showing symptoms when I was 5. (This was misdiagnosed as ADD. As was the style at the time.) Others never develop it.
It has been confirmed in at least one case "see Glenn Close schizophrenia relative" or something. I think genetic susceptibility IS involved in some cases and presumed to be a factor in many. But this all feels like splitting hairs on words describing probability ;-)
https://www.nhs.uk/mental-health/conditions/schizophrenia/ca...
Paul Meehl was associated with the hypothesis of schizotaxia and schizotypy in the 1960s, he believed the first was caused by a single dominant gene. Schizotaxia would cause you to have 'synaptic slippage' which would cause negative social learning which would cause you to develop as a schizotype, which is related to
https://en.wikipedia.org/wiki/Schizotypal_personality_disord...
Schizotaxia, for instance, makes you liable to paranoia, but if it makes you a bullying magnet in school and the authorities blow off your concerns and refuse to protect you you learn that they really are out to get you which has many kinds of negative impact on your development which leads you to become a schizotype who might further develop schizophrenia if you are unlucky.
Maybe 5% of the population is schizotypal, maybe 5% of those develop schizophrenia.
Schizotypy is a form of neurodivergence that is similar in prevalence to autism and ADHD but unlike the others there are not institutions in place to diagnose it so if you present as a schizotype to a therapist under distress they will probably say you have "adjustment disorder with depression|anxiety|conduct concerns" and if they get so far as to think there is a developmental problem they will probably think it is autism or adhd since those are fashionable to have. (So fashionable that people who don't know anything about psychodiagnosis self-diagnose with autism or ADHD but a person who reads about psychology as a hobby might take decades to have that fateful moment where they read a long list of 20+ signs and symptoms and find they have 15 of them... But the similarity to autism is apt since schizotypes develop 'special interests' and tend to be loners because they learn that it is completely unsafe to reveal their difference to other people, even if they have no idea what that difference is.)
It is not so safe to tell people you are a schizotype because of the stigma associated with schizophrenia and the fact that schizotypy is not well known among either the public or medical professionals. Some authorities think the pediatric syndrome described in this book
https://www.amazon.com/Loners-Life-Path-Unusual-Children/dp/...
is usually schizotypy.
ECT has always served to remove symptoms or “normalize” people by just frying them until they’re a hollow drone.
Drugs can be useful. I know many schizophrenic people are happy for their drugs. But we shouldn’t forget that “real schizophrenia” is impossible to model in mice (how do you model a terrible parental situation for example?). And more generally, we shouldn’t forget that schizophrenia is mostly social and psychological in origin, rather than purely biological. A drug can target some chemical that is present in this process, but the cause is not some exogenous chemical, so it does not treat the “real cause” (see e.g. The Myth of the Chemical Cure). Another way of saying this is that the biological system that needs to be modeled is really the holistic biological system of society, family, etc (can also be useful to think about this in a cybernetics kind of way—see e.g. Bateson who developed the “double bind” theory of schizophrenia).
Moral of the story, at least in my view: we should care and treat schizophrenic people with empathy and simultaneously aim to improve the social situations that induce schizophrenia. And how do we improve the social situations? Well, first, if needed, we just work on ourselves, our own self-respect, competence, moral agency, etc., and spread goodness to the people in our vicinity, whilst having faith that others who are quite equal to us and who we have no control over can do the same.
I get that some people really want to believe that everything affecting the mind must be psychogenic, but with schizophrenia you're seriously stretching it. Schizophrenia isn't just a psychiatric disorder, it's a heavy duty brain dysfunction.
Realigning the internal systems involved in schizophrenia seems at least as important as improving external systems that might provoke it.
Basically what I was indicating though, and which I get from for example, RD Laing and Gregory Bateson, is that the best “cure”, societally-willing, is to provide a safe community environment where the schizophrenia is allowed to “run its course”. I know capitalist societies always want a commoditized solution like a pill, and certainly those can be useful, but we shouldn’t forget that a more personal, human solution is always better.
Western medicine can also learn a lot from eastern medicine in this regard. Luckily there’s a lot of research being done on what the pros and cons of each system are. Definitely recommend the book The Web that Has No Weaver for example.
> And more generally, we shouldn’t forget that schizophrenia is mostly social and psychological in origin, rather than purely biological
I'd be curious if you could provide references for that.
> ECT has always served to remove symptoms or “normalize” people by just frying them until they’re a hollow drone.
ditto
Also recommend like I said Gregory Bateson’s work, or more recently books like The Myth of the Chemical Cure by Dr. Joanna Moncrieff.
The general point is that if we want to model causality we have to include the full system in question. If we narrow our perspective to an inner sub-system, then anything outside looks like an exogenous cause. But we may have to keep expanding wider and wider to get an accurate picture. Intervention can be done at any level of granularity, but the lower it is done, the more we’ll be missing on the root cause of damage, which is likely causing harm elsewhere too.
Psychiatric nurses have no patience full stop.
While it's not possible to completely decouple biological and social risk factors, my understanding of schizophrenia is in direct contradiction with your claim that it's primarily social.
As I understand it schizophrenia, the extremely high heritability strongly implicates biological factors. Beyond heritability, many of the other risk factors also implicate a biological basis, from microbe infections, drug use, and pre-natal biological stress (nutrition, maternal health, etc).
None of that contradicts the need to treat people suffering from schizophrenia with empathy, or to improve the social situations they're in, but I think your central claim about "mostly social" is wrong, and undermines the rest of your argument.
For example, it is more prevalent in urban environments, more prevalent among minorities in western countries, etc. it has better outcomes in “developing” countries.
Core human biology likely hasn’t changed much in recent history, so what had changed? Many of these factors that have changed, like drug use, are also very much related to social and economic factors. Of course these are all psychologically related and biologically related. But the point is we need to model the whole system, and focus on what has been changing if we want to get to root causes of change.